Management of high-risk (B3) breast lesions in symptomatic practice: evidence review and practical recommendations for multidisciplinary care
32 affiliations
- 1School of Medicine, University of Nottingham, Nottingham, UK
- 2Department of Pathology, National Reference Laboratory and Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
- 3Cellular Pathology, Queen Elizabeth Hospital Birmingham, Birmingham, UK
- 4Department of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
- 5Department of Pathology, University Hospitals Leuven, KU-Leuven, Herbstreit 49, Leuven, 3000 Belgium
- 6Discipline of Pathology, University of Galway, Galway, Ireland
- 7Breast Radiologist, Breast Unit, University of Galway, Galway, Ireland
- 8Oncoplastic Breast Surgery Department, The Royal Wolverhampton NHS Trust, Wolverhampton, UK
- 9Reference Centers Mammography, Münster and Berlin, Berlin, Germany
- 10Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
- 11Oncoplastic Breast Surgery Department, Broomfield Hospital, Mid and South Essex NHS Trust, Chelmsford, England
- 12Department of Histopathology, Addenbrookes Hospital, Cambridge, UK
- 13Department of Pathology, University Hospitals of Derby and Burton, Derby, UK
- 14Department of Surgery, NYULangone Health Medical Center, New York, NY USA
- 15Pathology and Laboratory Medicine Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
- 16Radiology Department, Northwick Park Hospital & Royal Free Breast Screening, Harrow, Middlesex UK
- 17Department of Pathology and Molecular Pathology, University Hospital Zurich, Zurich, Switzerland
- 18Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands
- 19Department of Pathology, Albert Szent-Györgyi Faculty of Medicine, University of Szeged, Bács-Kiskun County Teaching Hospital, Szeged, Kecskemét, Hungary
- 20Department of Biomedical and Neuromotor Sciences, Unit of Pathology at Bellaria Hospital, University of Bologna, Bologna, 40139 Italy
- 21Department of Pathology, Erasmus MC, Rotterdam, The Netherlands
- 22Department of Cellular Pathology, Barts Health NHS Trust, Queen Mary University of London, London, UK
- 23Department of Pathology, Liverpool University Hospitals Group, Liverpool, UK
- 24Pathology Department & Epithelial Stem Cells and Cancer Lab, CRCM, Inserm, CNRS, Institut Paoli-Calmettes, Aix-Marseille Univ, Equipe labellisée LIGUE contre le cancer, Marseille, France
- 25Research Department of Pathology, University College London, London, UK
- 26Department of Pathology, Medical University of Vienna, Vienna, Austria
- 27Department of Medical Sciences, University of Turin, Turin, Italy
- 28Surgical Department Breast Oncoplastic Unit, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates
- 29Department of Pathology, UCLouvain, Cliniques universitaires Saint-Luc, Brussels, Belgium
- 30Luma Medical Centre, Royal Square Medical Centre, Singapore, Singapore
- 31Department of Histopathology, School of Medicine, Irish National Breast Screening Programme, St. Vincent’s University Hospital, University College Dublin, Dublin, Ireland
- 32School of Cancer and Pharmaceutical Sciences, King’s College London, London, UK
Abstract
Borderline breast lesions (B3 lesions, also termed lesions of uncertain malignant potential or high-risk lesions) represent a heterogeneous group of entities associated with variable risks of malignancy. While the management of screen-detected B3 lesions has become increasingly standardised, no dedicated international recommendations exist for symptomatic B3 lesions, despite them posing a distinct clinical challenge. Symptomatic lesions differ from screen-detected lesions in their mode of presentation, lesion characteristics, biopsy techniques, and diagnostic objectives; consequently, management strategies derived from screening populations may not be directly applicable. This review summarises the current evidence and proposes a pragmatic management framework for B3 lesions encountered in the symptomatic setting (defined as those presenting with breast symptoms outside population-based screening programmes). This is particularly relevant for patients under 50 years of age, where the primary objective is to exclude malignancy at the index site rather than solely to stratify long-term cancer risk. Clinical-radiological-pathological concordance and multidisciplinary assessment are central to management decisions. Lesions presenting as palpable abnormalities (which are typically larger) or those demonstrating radiological-pathological discordance warrant a lower threshold for additional sampling or excision. Conversely, selected concordant lesions without atypia may be managed conservatively following adequate sampling. The long-term cancer risk associated with epithelial atypia should also be considered with subsequent risk-based surveillance implemented where appropriate. Overall, management requires a risk-adapted, multidisciplinary approach integrating pathological, radiological, and clinical factors alongside patient symptoms and quality-of-life considerations. Given the limited evidence, current recommendations rely on expert consensus and a proposed practical framework. They underscore the need for large-scale, high-quality studies with long-term follow-up to establish formal clinical guidelines.
Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s00428-026-04672-2.
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BibTeX
@article{rakha2026management,
title = {{Management of high-risk (B3) breast lesions in symptomatic practice: evidence review and practical recommendations for multidisciplinary care}},
author = {Emad A. Rakha and Abeer Shaaban and Giuseppe Floris and Grace Callagy and Nisha Sharma and Raghavan Vidya and Thomas Decker and Peter Regitnig and Yazan Masannat and Elena Provenzano and Rahul Deb and Jill R. Dietz and Basel Altrabulsi and William Teh and Muna A. Abuhejleh and Zsuzsanna Varga and Paul van Diest and Gábor Cserni and Maria Pia Foschini and Carolien H.M. van Deurzen and Madhuri Warren and Yasmeen Mir and Emmanuelle Charafe-Jauffret and Soha El Sheikh and Zsuzsanna Bago-Horvath and Isabella Castellano and Stephen Grobmyer and Mieke R. Van Bockstal and Puay Hoon Tan and Cecily Quinn and Sarah Pinder},
journal = {Virchows Archiv},
year = {2026},
month = aug,
doi = {10.1007/s00428-026-04672-2},
url = {https://doi.org/10.1007/s00428-026-04672-2},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Management of high-risk (B3) breast lesions in symptomatic practice: evidence review and practical recommendations for multidisciplinary care
AU - Emad A. Rakha
AU - Abeer Shaaban
AU - Giuseppe Floris
AU - Grace Callagy
AU - Nisha Sharma
AU - Raghavan Vidya
AU - Thomas Decker
AU - Peter Regitnig
AU - Yazan Masannat
AU - Elena Provenzano
AU - Rahul Deb
AU - Jill R. Dietz
AU - Basel Altrabulsi
AU - William Teh
AU - Muna A. Abuhejleh
AU - Zsuzsanna Varga
AU - Paul van Diest
AU - Gábor Cserni
AU - Maria Pia Foschini
AU - Carolien H.M. van Deurzen
AU - Madhuri Warren
AU - Yasmeen Mir
AU - Emmanuelle Charafe-Jauffret
AU - Soha El Sheikh
AU - Zsuzsanna Bago-Horvath
AU - Isabella Castellano
AU - Stephen Grobmyer
AU - Mieke R. Van Bockstal
AU - Puay Hoon Tan
AU - Cecily Quinn
AU - Sarah Pinder
PY - 2026
DA - 2026/08/10
JO - Virchows Archiv
DO - 10.1007/s00428-026-04672-2
UR - https://doi.org/10.1007/s00428-026-04672-2
AB - Borderline breast lesions (B3 lesions, also termed lesions of uncertain malignant potential or high-risk lesions) represent a heterogeneous group of entities associated with variable risks of malignancy. While the management of screen-detected B3 lesions has become increasingly standardised, no dedicated international recommendations exist for symptomatic B3 lesions, despite them posing a distinct clinical challenge. Symptomatic lesions differ from screen-detected lesions in their mode of presentation, lesion characteristics, biopsy techniques, and diagnostic objectives; consequently, management strategies derived from screening populations may not be directly applicable. This review summarises the current evidence and proposes a pragmatic management framework for B3 lesions encountered in the symptomatic setting (defined as those presenting with breast symptoms outside population-based screening programmes). This is particularly relevant for patients under 50 years of age, where the primary objective is to exclude malignancy at the index site rather than solely to stratify long-term cancer risk. Clinical-radiological-pathological concordance and multidisciplinary assessment are central to management decisions. Lesions presenting as palpable abnormalities (which are typically larger) or those demonstrating radiological-pathological discordance warrant a lower threshold for additional sampling or excision. Conversely, selected concordant lesions without atypia may be managed conservatively following adequate sampling. The long-term cancer risk associated with epithelial atypia should also be considered with subsequent risk-based surveillance implemented where appropriate. Overall, management requires a risk-adapted, multidisciplinary approach integrating pathological, radiological, and clinical factors alongside patient symptoms and quality-of-life considerations. Given the limited evidence, current recommendations rely on expert consensus and a proposed practical framework. They underscore the need for large-scale, high-quality studies with long-term follow-up to establish formal clinical guidelines. Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s00428-026-04672-2.
SN - 0945-6317
SN - 1432-2307
ER -